|Year : 2007 | Volume
| Issue : 1 | Page : 26-29
Stavudine vs. Zidovudine as antiretroviral therapy
Ajay Sharma, Megha Modi, Archana Sharma, YS Marfatia
Department of Skin and VD, Medical College and SSG Hospital, Vadodara, India
Y S Marfatia
Department of Skin and V.D., Govt. Medical College and SSG Hospital, Vadodara - 390 001
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Stavudine (d4T) and zidovudine (AZT) belong to nucleoside reverse transcriptase inhibitor (NRTI) group of drugs and they are the core drugs with lamivudine (3TC) as the first-line therapy. d4T is reported to cause a number of long-term metabolic and morphologic adverse drug reactions (ADR). In this study, the incidence and pattern of ADR due to d4T and AZT were compared.
Ninety cases on antiretroviral treatment (ART) were studied prospectively over a period of 2 years. Forty-two cases were on AZT-based regimen, and 48 cases were on d4T-based regimen. In all cases, baseline investigations, serum lipid profile and lactate levels (if required) were carried out. Cases were evaluated monthly, and investigations were repeated quarterly for any ADR.
Out of the 42 cases on AZT-based regimen, 21 had ADR; while 23 out of the 48 cases on d4T had ADR. Anemia (42.8%) and nail hyperpigmentation (30.9%) were the commonest ADR due to AZT. Peripheral neuropathy (PN) (39.6%) was the commonest ADR with d4T, followed by lipodystrophy (LD) (22.9%). Change of therapy was required in 1 case on AZT with severe anemia and in 5 cases on d4T with LD, PN or lactic acidemia.
The severe ADR with d4T needed a change of regimen to AZT in 5 cases. Moreover, d4T requires monitoring for long-term metabolic changes, which may lead to morphologic disfigurement which are particularly distressing to females. As the cost of both the regimens is now almost equal, preference should be given to AZT-based regimen.
Keywords: Adverse drug reactions, acquired immunodeficiency syndrome, zidovudine, stavudine
|How to cite this article:|
Sharma A, Modi M, Sharma A, Marfatia Y S. Stavudine vs. Zidovudine as antiretroviral therapy. Indian J Sex Transm Dis 2007;28:26-9
|How to cite this URL:|
Sharma A, Modi M, Sharma A, Marfatia Y S. Stavudine vs. Zidovudine as antiretroviral therapy. Indian J Sex Transm Dis [serial online] 2007 [cited 2020 Apr 5];28:26-9. Available from: http://www.ijstd.org/text.asp?2007/28/1/26/35708
| Introduction|| |
Stavudine (d4T) and zidovudine (AZT) belong to nucleoside reverse transcriptase inhibitor (NRTI) group of drugs, and they are the core drugs with Lamivudine (3TC) as the first-line treatment. The major medium- to long-term toxicities of NRTI therapy are thought to be secondary to inhibition of mitochondrial DNA polymerase gamma, resulting in impaired synthesis of mitochondrial enzymes that generate ATP by oxidative phosphorylation.  These include myopathy (zidovudine), neuropathy (stavudine, didanosine), hepatic steatosis and lactic acidemia (didanosine, stavudine, zidovudine), and possibly also peripheral lipoatrophy (predominantly with stavudine). The most serious mitochondrial toxicities are lactic acidosis and pancreatitis; mortality was 80% in patients with lactate concentrations greater than 10 mmol/L. Although lactic acidosis is rare, lactic acidemia is far more common (about 15%) and is often associated with mild constitutional symptoms, mild increase in liver enzymes and peripheral lipoatrophy.  AZT may be superior to d4T because its active triphosphate is only a weak inhibitor of gamma polymerase.
Anemia and granulocytopenia affect about 5-10% of patients who receive AZT and are more common in those with more advanced HIV disease. 
Earlier, d4T-based ART regimen was the cheapest and the most frequently prescribed therapy in resource-restricted setup. Nonetheless, d4T is reported to cause a number of long-term metabolic and morphologic ADR.
| Materials and Methods|| |
This study was carried out in the HIV referral clinic, Department of Skin and V.D., S.S.G. Hospital and Medical College, Vadodara, during the period from Sept. 2004 to Oct. 2006. Ninety HIV-positive cases on Antiretroviral Treatment (ART) were included in the study. A detailed history of every patient was taken, including past history of ART. History of fever, cough, breathlessness, pulmonary/ extrapulmonary tuberculosis (TB) [past or present], skin lesions, mucosal lesions and sexually transmitted diseases (STD) was elicited from every patient.
Baseline laboratory investigations such as hemoglobin, total count, differential count, ESR, urine (albumin, sugar and microscopic examination), venereal disease research laboratory (VDRL) test, HBsAg, mantoux test and fine needle aspiration cytology (FNAC) of lymph nodes were carried out in each patient. X-ray chest (PA view) and USG abdomen were done in all cases to find out focus of tuberculosis. Lymphocyte enumeration was carried out before starting anti-Koch's treatment (AKT), and viral load was not advised routinely. They were also subjected to liver function tests (LFTs), renal function tests (RFTs), lipid profile and blood sugar.
AZT- and d4T-based regimens were prescribed in 42 and 48 cases respectively. They were combined with 3TC and one non-nucleoside reverse transcriptase inhibitor (NNRTI).
All cases on ART were subjected to clinical and laboratory monitoring periodically. Patients were screened for opportunistic infections (OIs) and drug toxicity on each visit. CD4 count was done 6 monthly. In cases on AZT-based regimens, hemoglobin was measured before initiation and at weeks 4, 8 and 12 on therapy or in response to symptoms. Liver function tests, lipid profile, serum lactate, serum amylase were done whenever indicated. Adherence to study medication was assessed based on patients' self report. They were asked to bring empty bottles and strips.
| Results|| |
Out of the 42 cases on AZT, 21 cases (50%) developed ADR; while 23 (47.9%) out of the 48 cases on d4T developed ADR. Anemia was the most common AZT-induced ADR (42.8%), followed by nail hyperpigmentation (30.9%) [Figure - 1], oral hyperpigmentation (7.2%) and fatty changes in liver (7.2%) [Table - 1]. Grade IV anemia with hemoglobin <6.5 gm% was observed in 3 cases (7.2%) [Table - 2]. Macrocytosis was observed in 8 (19%) cases, which is also an indicator of adherence to ART.
Most common ADR due to d4T was PN, observed in 39.6% cases; followed by LD in 22.9% cases [Table - 1]. Lactic acidemia was observed in 1 case only. d4T-induced PN was observed at a mean CD4 count of 69 in males and 144 in females [Table - 3]. Lipodystrophy was observed in 11 cases on d4T. Increase in abdominal fat and loss of buccal fat were most commonly observed [Table - 4], [Figure - 2].
Change of therapy was required in one case on AZT with severe anemia and five cases on d4T with either LD or PN or lactic acidemia [Table - 5].
| Discussion|| |
The incidence of ADR was almost equal with both AZT and d4T (50% vs. 47.9%), but more serious ADR were observed with d4T.
Dournon et al . reported AZT-induced anemia in 16.15% cases; while in the present study, it was observed in 42.8% cases.  Eighteen cases had anemia; and in one case, AZT was changed to d4T (grade IV anemia). Van Leeuwen et al . reported severe anemia (<6 gm/dl) in 34% cases; while in the present study, it was observed in 7.2% cases.  Rest of the cases were managed with iron and folic acid supplementation. Thierry Saint Marc et al . reported AZT-induced LD in 18.75% cases; while in the present study, it was observed in 4.8% cases.  Three cases developed fatty changes in liver, which were detected on ultrasonography.
The most common adverse drug reaction due to d4T was PN, observed in 39.6% cases, followed by LD in 22.9% cases. H. Brett Smith et al . reported d4T-induced PN and LD in 24% and 16% cases respectively.  Thierry Saint Marc et al . reported LD in 63% cases. In the present study, male cases developed peripheral neuropathy at lower CD4 count than did female cases. Moyle et al . reported that d4T-induced PN is more common at CD4 count <100 cells/mm 3 . 
Increase in abdominal fat and loss of buccal fat were observed with d4T. Morphologic changes seem to occur more commonly in women than in men (41.9% vs . 29.5% in a study of 2,250 HIV-infected patients), and women on Highly Activated Anti Retroviral Treatment experience more fat accumulation (in breast and abdomen) while men present more likely with fat loss (in limb and buttock). 
The severity of ADR with d4T needed a change of regimen to AZT. Moreover, d4T requires monitoring for long-term metabolic changes, which may lead to morphologic disfigurements that are particularly distressing to females. Lactic acidemia was observed in one case. Strong suspicion helped in early diagnosis and prompt management.
As the cost of both the regimens is now almost equal, preference should be given to AZT-based regimen.
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[Figure - 1], [Figure - 2]
[Table - 1], [Table - 2], [Table - 3], [Table - 4], [Table - 5]